Defeating the Silent Enemy: Antimicrobial Resistance Looming as the Next Global Pandemic.

Antibiotics are the magic bullets that have saved millions worldwide. Enormous and irresponsible use of antibiotics has led to resistance to antibiotics, which is a matter of global health concern. The superbugs are responsible for life-threatening infections, treatment failure, and high mortality worldwide. The urgent healthcare threat caused by antimicrobial resistance (AMR) to nonfermenting gram-negative bacteria is being increasingly acknowledged worldwide. Antibiotic resistance found in organisms in hospital settings is now increasingly found in the community. Although antimicrobial stewardship requiring a multidisciplinary approach is developing rapidly at the hospital level, it needs more attention at the community level. New therapeutics are certainly required, but the major challenge is rapidly identifying resistant infections and tailoring treatment. This review highlights the crisis that reflects the current scenario of AMR, common resistant pathogens, and the major challenges in the fight against AMR. It also discusses potential methods and strategies to address the intricacies of antibiotic resistance.

A Comparative Analysis of the Efficacy and Safety of Nimesulide/Paracetamol Fixed-Dose Combination With Other NSAIDs in Acute Pain Management: A Randomized, Prospective, Multicenter, Active-Controlled Study (the SAFE-2 Study).

Objective In this study, we aimed to compare the efficacy and safety of the fixed-dose combination (FDC) of nimesulide (100 mg) + paracetamol (325 mg) [NP], ketorolac (10 mg) [Kt] alone, diclofenac (50 mg) + paracetamol (325 mg) [DP], and aceclofenac (100 mg) + paracetamol (325 mg) [AP] in patients with acute painful conditions. Methods This was a randomized, prospective, open-label, multicentre, active-controlled study involving patients aged ≥18 years, with acute painful conditions like low back pain, acute musculoskeletal disorders, and trauma such as tendinitis, tenosynovitis, bursitis, sprains and strains, migraine, dental pain, painful dental procedures, and post-surgical pain. Reduction in pain intensity and liver, renal, gastrointestinal, and cardiovascular safety were assessed on days seven and 14. Results A total of 600 patients were randomized into NP, Kt, DP, and AP groups in a 1:1:1:1 ratio. NP, DP, and AP were administered twice a day while Kt was given three times a day. The reduction of pain as measured by the numerical rating scale (NRS) scores at the end of day seven was 3.75 ± 1.58 in the NP group, 2.96 ± 1.18 in the Kt group, 3.42 ± 1.42 in the DP group, and 3.47 ± 1.30 in the AP group. The pain reduction in the NP group was significantly greater (p<0.001) as compared to the Kt group and non-inferior to the DP and AP groups on days seven and 14. Non-inferiority was concluded between the NP, DP, and AP groups as the lower limit of 95% CI of the difference in the change of pain intensity on both days seven and 14 was above the predefined margin of -1.0. All the drugs were well tolerated, but a significantly greater number of adverse events were reported in the DP group (32) as compared to the NP group (14) (p<0.05). The most common adverse events reported during the study were nausea, gastritis, and abdominal pain in all four groups. There was no significant alteration in liver and renal function tests except a rise in serum creatinine in the DP group. Conclusions The FDC of nimesulide with paracetamol is superior to ketorolac and non-inferior to the FDC of diclofenac with paracetamol and aceclofenac with paracetamol in the management of pain in patients with acute painful conditions. The tolerability profile of the FDC of nimesulide with paracetamol is similar to that of ketorolac but better than diclofenac with paracetamol and aceclofenac with paracetamol combinations.

Long-Term Use of Proton-Pump Inhibitors: Unravelling the Safety Puzzle.

Globally, over 25% of the population suffers from acid-related disorders such as dyspepsia or gastroesophageal reflux disease (GERD), and around 7.6% of Indians report having GERD symptoms on a frequent enough basis to warrant a diagnosis. Over the past three decades, proton-pump inhibitors (PPIs) have been the mainstay of medical therapy for acid-peptic diseases like GERD, etc. Additionally, they are frequently prescribed for prophylactic purposes and in conjunction with non-steroidal anti-inflammatory drugs. PPIs are generally prescribed for four to eight weeks. However, it may be prescribed for patients with comorbidities and multiple medications for a longer period of time. While this remains true in terms of effectiveness, concerns have been raised about the safety of long-term PPI use and the serious adverse effects that may result. Some of the observational and population-based cohort studies have shown an association between long-term use of PPIs and an increased risk of pneumonia, major cardiovascular events, dementia, vitamin B12 deficiency, bone fractures, gastric cancer, and kidney injury, among others. This review analyzes the clinical data supporting the long-term use of PPIs and takes a deep dive into whether these several emerging long-term concerns apply to the currently available PPIs in India. We have summarized a vast array of studies, including randomized trials, cohort studies, and meta-analyses, that report low or high incidences of major health risks linked with PPIs and have assessed their appropriateness over a given period.

In Vitro Susceptibility of Clinical Isolates to Ceftriaxone Alone and Ceftriaxone in Combination With Sulbactam or Tazobactam: A Comparative Study of Broad-Spectrum ß-Lactam Antibiotics in India.

Background This study was designed to evaluate the current in vitro susceptibility of clinical isolates to broad-spectrum ß-lactam antibiotics. Methodology Bacterial isolates, cultured from 180 non-repetitive clinical samples between April and November 2022 at three hospitals in India, were used to evaluate the minimum inhibitory concentration (MIC) of broad-spectrum ß-lactam antibiotics using the Epsilometer test (E-test) method. Test antibiotics were ceftriaxone and ceftriaxone in combination with ß-lactamase inhibitors (BLIs) sulbactam and tazobactam. Comparator antibiotics included amoxicillin + BLI clavulanic acid, piperacillin + tazobactam, cefotaxime, and cefepime. The MIC values obtained were used to assess the susceptibility of the isolates and to compute the efficacy ratios (ERs) of the antibiotics. Results Among the 180 clinical isolates, ~89% were gram-negative bacteria, the most prevalent ones being Escherichia coli and Klebsiella pneumoniae. Of the gram-negative isolates, ~37% were susceptible/intermediately susceptible to ceftriaxone, and ~29% were susceptible to ceftriaxone + BLIs. The test antibiotics had ER >10 against 85%-95% E. coli isolates, whereas comparator antibiotics had ER >10 against 31%-68% isolates. The differences between the test antibiotics and piperacillin + tazobactam or cefotaxime were statistically significant. Ceftriaxone, ceftriaxone + sulbactam, and ceftriaxone + tazobactam had ER >10 against 78%, 100%, and 90% of K. pneumoniae isolates, while the corresponding percentages for cefotaxime, piperacillin + tazobactam, and cefepime were 100%, 64%, and 80%, respectively. The difference between ceftriaxone + BLIs and piperacillin + tazobactam was statistically significant. Ceftriaxone + BLIs had ER >10 against all E. coli isolates producing extended-spectrum ß-lactamases (ESBLs); the percentage of isolates was significantly higher than that for piperacillin + tazobactam. Ceftriaxone + tazobactam had ER >10 against all ESBL-producing K. pneumoniae isolates; ceftriaxone and ceftriaxone + sulbactam had ER ranging 6-10. Conclusions Ceftriaxone and ceftriaxone in combination with sulbactam and tazobactam are promising antibiotics to explore against prevalent infectious microorganisms such as E. coli and K. pneumoniae. Ceftriaxone + tazobactam also holds promise against ESBL-producing variants.

An Open-label, Prospective, Multicentric, Cohort Study of Nimesulide/Paracetamol Fixed Drug Combination for Acute Pain Management: Sub-group Analysis.

OBJECTIVE: Nimesulide has been evaluated in numerous clinical studies in the management of a variety of acute painful conditions. However, there is limited Indian data available on the nimesulide/paracetamol fixed drug combination (FDC). Hence, an open-label prospective multicentric study was conducted to evaluate the safety and efficacy of this FDC in the management of acute painful conditions in real-world settings. MATERIALS AND METHODS: A prospective, open-label, and multicenter study conducted at 24 centers across Indian patients with acute painful conditions due to trauma, tendinitis, myalgia, low backache, sprains, pulled muscle, soft tissue injury, dental pain, and dental procedure/surgery. Nimesulide/paracetamol FDC was prescribed by clinicians as a part of routine practice. The effectiveness was evaluated on the numerical rating scale (NRS), that is, pain intensity at rest and movement, and the physician/patient global assessment scale (GAS) among the subgroups of acute painful conditions like myalgia, dental pain, low backache, etc. Hepatic safety was also evaluated among the subgroups at the end of treatment. RESULT: A total of 464 patients were included in the study. The reduction in NRS score at rest and movement during treatment duration across different types of pain was statistically significant (p < 0.001). Pain reduction was evident as per patient and physician GAS at the end of treatment in all indications. No clinically significant difference was found in liver parameters at the end of the study. Nimesulide/paracetamol (FDC) was well tolerated across all the subgroups. CONCLUSION: Nimesulide/paracetamol FDC was found to be well-tolerated and effective in pain management across all acute painful conditions in a real-world setting without any hepatic safety concerns.

Correction to: Efficacy and Safety of Biosimilar Romiplostim Versus Innovator Romiplostim in Patients with Chronic Immune Thrombocytopenia.

[This corrects the article DOI: 10.1007/s12288-022-01602-5.].

Efficacy and Safety of Biosimilar Romiplostim Versus Innovator Romiplostim in Patients with Chronic Immune Thrombocytopenia.

Romiplostim is a Food and Drug Administration (FDA)-approved therapy for immune thrombocytopenia (ITP). Biosimilar is a biological product that has no clinical meaningful difference from an existing FDA-approved reference product. It has a potential of lowering health-care-related cost. Biosimilar of romiplostim can be made available to patients with ITP at a low cost and can be beneficial in providing the best therapy. Thus, the efficacy and safety of biosimilar romiplostim (ENZ110) was compared with innovator romiplostim (Nplate) with respect to platelet response in patients with chronic ITP. This was a prospective, multicenter, randomized, and double-blind clinical trial. Patients with chronic ITP, aged 18-65 years, were enrolled in a study and were randomized to receive either ENZ110 or Nplate in a 3:1 ratio for a treatment period of 12 weeks, respectively. After completion of the treatment period, the patients were followed-up for one week to evaluate the platelet response and to monitor the adverse events (AEs). Over the duration of 12 weeks, platelet response of > 50 × 109/L was achieved in 85.3% patients treated with ENZ110 and in 75.0% patients treated with Nplate in per protocol population. In intent-to-treat population, 83.8% patients with ENZ110 and 76.9% patients with Nplate achieved a platelet response of > 50 × 109/L. In the ENZ110 group, 111 AEs were recorded in 66.7% patients, while 18 AEs were reported in 61.5% patients in the Nplate group. The study demonstrated non-inferiority with comparable efficacy and safety between biosimilar romiplostim and innovator romiplostim in patients with chronic ITP. Trial registration number and date of registration: CTRI/2019/04/018614.

An In Vitro Susceptibility Study of Cefotaxime-Sulbactam on Clinical Bacterial Isolates From Various Regions in India: A Comparison With Ceftriaxone-Sulbactam.

Background and objective Combining sulbactam with cefotaxime/ceftriaxone augments its antimicrobial activity against ß-lactamase-producing bacteria. They are widely used as empirical treatment for many clinical infections. However, there is a scarcity of data on the susceptibility of various organisms to these antibiotics in the Indian region. In light of this, the present in vitro study evaluated the susceptibility of bacterial isolates to cefotaxime-sulbactam and compared it with ceftriaxone-sulbactam. Methodology Clinical samples with positive bacterial cultures from various laboratories in India were subjected to antibiotic sensitivity testing using in vitro E-test strips and disk diffusion methods to determine the minimum inhibitory concentration (MIC) and zone of inhibition (ZOI), respectively. MIC50 and MIC90 values were determined along with the measurement of the ZOI for the effectiveness of antibiotics. Interpretations of MIC and ZOI values were made as per the criteria set by the Clinical and Laboratory Standards Institute (CLSI) guidelines to estimate the proportion of sensitive organisms. Results Among 400 clinical isolates evaluated, Escherichia coli (E. coli) (47.75%) was the most common organism isolated followed by Klebsiella (26%), Salmonella (7.75%), Proteus (3.8%), and Acinetobacter (2.8%). The mean ZOI was found significantly higher for E. coli, Klebsiella, and Salmonella in the cefotaxime-sulbactam group than in the ceftriaxone-sulbactam group. MIC50 values for E. coli and Klebsiella were 0.25 and 0.19 µg/ml, respectively in the cefotaxime-sulbactam group as compared to 0.38 and 0.25 µg/ml, respectively for ceftriaxone-sulbactam. The proportion of sensitive isolates was also higher in the cefotaxime-sulbactam group for E. coli, Klebsiella, and Salmonella. Conclusions The in vitro effect of cefotaxime-sulbactam on organisms is similar to that of ceftriaxone-sulbactam in terms of MIC, ZOI, and proportion of sensitivity based on our study involving clinical isolates from various parts of India. Cefotaxime-sulbactam may be preferred in the empirical management of various clinical infections.

Etiological Patterns, Liver Fibrosis Stages and Prescribing Patterns of Hepato-Protective Agents in Indian Patients with Chronic Liver Disease.

OBJECTIVE: Considering the paucity of relevant data for chronic liver disease (CLD) from India, this PAN-India study was conducted to assess the current etiologic spectrum of CLD, stage of liver fibrosis at presentation and the prescribing patterns of hepato-protective agents by gastroenterologists in Indian real-world setting. This data would aid in early detection and formulation of effective management strategies for CLD in India. MATERIALS AND METHODS: In this cross-sectional, multicentric, epidemiological study, consecutive patients (18 ≥ 65 years) diagnosed with CLD, assessed for liver fibrosis by Vibration Controlled Transient Elastography (VCTE), were evaluated for etiology by standard clinical and laboratory criteria and grouped in to alcoholic liver disease (ALD)/non-alcoholic fatty liver disease (NAFLD)/viral liver disease/ drug induced liver injury (DILI)/others. The doctors' prescription was studied in each case to note the pattern of hepatotropic medications prescribed, in addition to other specific agents. RESULTS: Out of 504 enrolled patients with CLD (mean age: 47.9±11.81 years; men: 67.9%), 39.7% had NAFLD, 25.6% had ALD, 17.5% had hepatitis B (HBV), 7.9% had hepatitis C (HCV), 1.6% had autoimmune hepatitis, 0.4% had DILI and 7.3% had other causes of liver disease. Diabetes (15.9%), hypertension (12.9%), hypothyroidism (3.0%), dyslipidemia (1.2%) and obesity (0.4%) were the commonly reported comorbidities. Liver stiffness corresponding to the diagnosis of F4 liver fibrosis stage was reported in 77.5% HCV, 62.0% ALD, 46.0% NAFLD and 37.5% HBV patients. About 12.5% HCV, 8.0% NAFLD, 5.4% ALD, and 1.1% HBV patients reported F3 liver fibrosis stage. About 38.3% patients were on hepatoprotective drugs; commonly prescribed drugs were ademetionine (23.8%), ursodeoxycholic acid (17.9%) and drugs of herbal origin (11.3%). CONCLUSION: NAFLD is emerging as a predominant etiology of CLD in India, followed by ALD, HBV, and HCV. However, significant regional differences regarding predominant etiology was noted within the country. It was further noted that significant number of patients had advanced fibrosis based on VCTE assessment. This study emphasizes the need for appropriate risk evaluation and early assessment of severity of liver disease, for adequate disease management.

Animal models of erectile dysfunction.

Animal models have contributed to a great extent to understanding and advancement in the field of sexual medicine. Many current medical and surgical therapies in sexual medicine have been tried based on these animal models. Extensive literature search revealed that the compiled information is limited. In this review, we describe various experimental models of erectile dysfunction (ED) encompassing their procedures, variables of assessment, advantages and disadvantages. The search strategy consisted of review of PubMed based articles. We included original research work and certain review articles available in PubMed database. The search terms used were "ED and experimental models," "ED and nervous stimulation," "ED and cavernous nerve stimulation," "ED and central stimulation," "ED and diabetes mellitus," "ED and ageing," "ED and hypercholesteremia," "ED and Peyronie's disease," "radiation induced ED," "telemetric recording," "ED and mating test" and "ED and non-contact erection test."

Knowledge, attitude, and practices toward ayurvedic medicine use among allopathic resident doctors: A cross-sectional study at a tertiary care hospital in India.

CONTEXT: Ayurveda is most commonly practiced form of complementary and alternative medicine (CAM) in India. There are very few studies showing the knowledge, attitude, and practices (KAP) of allopathic doctors about Ayurvedic drugs and its use. AIMS: The study was initiated to assess KAP toward Ayurvedic medicine use among allopathic resident doctors. SETTINGS AND DESIGN: Cross-sectional and prospective study. MATERIALS AND METHODS: After obtaining permission from the Institutional Ethics Committee, allopathic resident doctors from clinical departments were approached personally. They were given pre-formed validated questionnaire to assess KAP toward Ayurvedic medicine use. STATISTICAL ANALYSIS USED: Descriptive statistics. RESULTS: Allopathic residents had little knowledge about basic concepts of Ayurveda, that is, 'panchakarma' and 'tridosha'. Majority residents (99%) had no opportunity to learn basics of Ayurveda, but 67% residents prescribed Ayurvedic medicines to patients. However, many residents (76%) mentioned that cross practice should not be allowed due to lack of knowledge. One resident knew that cross-practice was not allowed by law. The commonly prescribed proprietary Ayurvedic medicines were Liv-52 (39%), Shatavari (13%), Cystone (12%) and common ailments for which these medicines prescribed were liver disorders (34%), arthritis (18%), cough and cold (13%), kidney stones (11%), and piles (10%). Nearly 76% residents felt incorporation of Ayurveda with modern medicine would attract more patients and at the same time most residents (92%) agreed that Ayurvedic medicines need scientific testing before use. Though 50% of the residents agreed for voluntary training in Ayurveda, 80% denied compulsory training. Nearly 63% residents recommended Ayurveda among all CAMs. Most of residents heard of Ayurveda from their colleagues. CONCLUSIONS: This study reveals that allopathic resident doctors had little knowledge about Ayurveda and Ayurvedic medicine use but engaged in prescription of Ayurvedic medicines. So some interventions should be taken to increase the knowledge and awareness of allopathic resident doctors about Ayurvedic medicine use.

Awareness about medical research among resident doctors in a tertiary care hospital: A cross-sectional survey.

CONTEXT: Every medical practitioner should strive to contribute to the generation of evidence by conducting research. For carrying out research, adequate knowledge, practical skills, and development of the right attitude are crucial. A literature review shows that data regarding knowledge, attitude, and practices toward medical research, among resident doctors in India, is lacking. AIMS: This study was conducted to assess research-related knowledge, attitude, and practices among resident doctors. SETTINGS AND DESIGN: A cross-sectional survey was conducted using a pretested, structured, and pre-validated questionnaire. MATERIALS AND METHODS: With approval of the Institutional Ethics Committee and a verbal consent, a cross-sectional survey among 100 resident doctors pursuing their second and third years in the MD and MS courses was conducted using a structured and pre-validated questionnaire. STATISTICAL ANALYSIS: Descriptive statistics were used to analyze the results. RESULTS: The concept of research hypothesis was known to 58% of the residents. Ninety-eight percent of the residents were aware of the procedure to obtain informed consent. Seventy-six percent agreed that research training should be mandatory. Although 88% of the residents were interested in conducting research in future, 50% had participated in research other than a dissertation project, 28% had made scientific presentations, and only 4% had publications. Lack of time (74%), lack of research curriculum (42%), and inadequate facilities (38%) were stated as major obstacles for pursuing research. CONCLUSIONS: Although resident doctors demonstrated a fairly good knowledge and positive attitude toward research, it did not translate into practice for most of them. There is a need to improve the existing medical education system to foster research culture among resident doctors.